Sodium pump in the cardiac cytoplasmic membrane is essential for the generation and maintenance of transmembrane electro-chemical gradients and hence for the maintenance of excitability of cardiac cells. The effects of myocardial ischemia on the functional activity of sodium pump are not understood. Digitalis has been demonstrated to inhibit cardiac Na ion , K ion -ATPase and sodium pump activity and produce arrhythmias. The effects of myocardial ischemia on the cellular actions of digitalis have not been extensively studied, although increased incidences of arrhythmias have been reported with the use of digitalis in ischemic myocardium. The primary objective of this proposed research is to determine the effects of myocardial ischemia on the molecular mechanism of action of digitalis. This will be achieved by studying the effects of myocardial ischemia on sodium pump activity (as monitored by ouabain-sensitive 86Rb uptake) as well as on the molecular interaction between the digitalis and its "receptor" using cardiac Na ion, K ion -ATPase and sodium pump as the molecular model for the receptor. In addition, the effects of other biochemical derangements accompanied myocardial ischemia, such as cationic shifts and elevation of circulating levels of catecholamine, on the cardiac response to digitalis will also be studied. The second objective of this proposed research is to determine the effects of digitalis on the extent of myocardial ischemic injury following coronary artery occlusion. The severity of myocardial ischemic injury will be assessed by both indirect (epicardial ST-segment recording) and direct methods (myocardial creatine phosphokinase determinations and nitro-blue-tetrazolium staining methods).